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Cytology of bone lesions
1. CYTOLOGY OF BONE LESIONS
PRESENTER – DR. PREETI
MODERATOR – DR. HEMALATHA A
2. Classification of bone tumors
Aspiration techniques
Inflammatory conditions
Osteoid forming lesions
Cartilage forming tumors
Giant cell containing lesions
Cystic lesions of bone
Small cell neoplasms of bone
Bony lesions composed predominantly of spindle shaped cells.
Secondary metastasis to bone
Ancillary tecniques
Syndromes associated with bone tumors
7. Uses of fnac bone
The procedure is less traumatic than either CNB or open biopsy
Used safely in difficult sites such as vertebrae or pelvic bone
Allows rapid triage with coordination of further investigations and planning of anticipated therapy
Advantage of using CT GUIDED - needles can be directed to various parts of a large
heterogeneous mass for a more thorough and representative sampling
8. Clinical features
H/ O pain , progressive swelling
Fracture
Discharging sinus
Limping
Restriction of the movements
11. Complications of FNA of the Bone
Pneumothorax following needling of tumors in the ribs
Neurologic sequel to needling of lesions in the vertebrae
12. Normal structures seen on cytology
of bone
Osteoblasts
Osteoclasts
Chondrocytes
Cartilage
Hematopoietic tissue
19. Case - 1
A 15 year old boy comes to the opd with h/o
swelling and redness just below the knee with
pain in the knee since 5 days and h/o fever
since 3 days.
X – ray was taken and it showed - area of
periosteal proliferation surrounded by
successive layers of condensed cortical bone .
21. Osteomyelitis
KEY FEATURES
1. Abundant neutrophils , macrophages and necrotic bone (acute)
2. Granulomatous process with Epithelioid cell granulomas and Occasional giant cells of
Langerhans type
3. Tuberculous osteomyelitis is due to hematogenous spread from the lungs.
4. The most common sites are the vertebra followed by pelvic bones and the knee
Differential diagnosis: Langerhans cell histiocytosis
23. Fracture Callus
It’s a Reactive osteoblastic proliferation
misdiagnosed as malignant bone neoplasm, commonly osteosarcoma (OS).
Reactive osteoblasts in callus may display considerable pleomorphism with anisokaryosis
and hyperchromatic nuclei with prominent nucleoli .
Their chromatin pattern is quite regular, and the cytoplasmic “hof” is often visible in some
cells.
Clinical and radiologic correlation is essential to distinguish fracture callus from OS.
24. Cytological features
Fracture callus. (a and b)
Clusters of reactive
osteoblasts with anisokaryosis
Hyperchromatic nuclei
embedded in osteoid-like
matrix (MGG)
25. Case – 2
A 22 year old man with history of dull aching
pain in the neck since 1year
On NSAIDs
X – Ray - shows a well-circumscribed
radiolucent lesion in the bony cortex, with a
thin shell of peripheral new bone separating it
from the surrounding soft tissue
27. Osteoblastoma
Differential diagnosis: Osteosarcoma
Cytological features
1. Smears are moderately cellular , with a bloody background.
2. There is large number of plasmacytoid cells with eccentric nuclei that appear to protrude
from the cell.
3. Osteoclastic giant cells with upto 20nuclei per cell are visible.
4. Spindle cell aggregates occur in which the cells show no significant nuclear atypia.
5. Fragments of pink osteoid surrounded by osteoblast- like cells seen.
6. Mitotic figures are rare to absent in smear preparations.
29. Differential diagnosis
OSTEOID OSTEOMA OSTEOBLASTOMA AGGRESSIVE OSTEOBLASTOMA
< 1.5 CMS > 1.5 CMS > 4 CMS
M/C – Long bones of lower
extremity (femur neck) , rarely in
small bones of hands & feet
Axial skeleton (vertebrae ,sacrum
,craniofacial bones)
Teenage and young adults 2nd decade
M: F - 3 :1 M: F - 3 :1
Cytology not done Osteoblasts seen and No mitosis /
atypia on cytology
Epithelioid osteoblasts , nuclear
pleomorphism and occasional
mitosis.
Dull pain worse at night and
disappearce within 20 – 30 minutes.
Pain of varying intensity – 2 yrs
30. Case - 3
A 15 year old boy with h/o weight loss and
slow growing mass in the left shoulder since
3 years
X- ray – showing densely sclerotic lesion with
cloudy opacities and irregular , ill-defined
borders. Cortex destroyed. The arrow
pointing to codmans triangle.
32. Osteosarcoma
Osteosarcoma (OS) is a primary bone tumor composed of cells, which at least focally
produce osteoid
80% to 90 % of cases of OS are of the conventional highly malignant type.
Majority of them occur around the knee followed by the humerus and pelvic bones
Presentations - bone mass, often with a soft tissue involvement and pain
33. Osteoblastic subtype
( a and b )
Large, atypical tumor cells with round
to oval, irregular nuclei, a moderate
amount of cytoplasm,and large
macronucleoli (MGG).
( c ) Poorly cohesive clusters of
pleomorphic cells, some with atypical
mitoses and admixture of
osteoclasts(H&E).
( d ) Pleomorphic tumor cell
resembling osteoblast and a small
fragment of the bone.
( e ) Calcification seen in liquid-based
preparations (H&E; ThinPrep)
34. Cytologic features of osteosarcoma:
2. CHONDROBLASTIC SUBTYPE
Myxoid background matrix (red; red violet in MGG)
Fragments of hyaline cartilage
Cartilage with atypical chondrocytes in lacunae
Atypical mono- or binucleated chondroblasts
Admixture of similar cell population as in osteoblastic osteosarcoma in variable
proportions
35. Chondroblastic osteosarcoma
Large, atypical tumor cells( a ) adjacent
to the cartilaginous matrix or dispersed in
the myxoid and chondroid background
matrix
( b and c ), which is more abundant than
osteoid matrix. Note tumor cells
resembling osteoblasts and mitoses
(MGG).
( d ) Malignant cartilage with atypical
chondroblasts embedded in a chondroid
matrix (H&E)
36. Giant cell-rich osteosarcoma
(a–c) Smears resembling giant
cell tumor but clearly
pleomorphic tumor cells consist
with highly malignant neoplasm
(H&E).
(d) Positive alkaline
phosphatase staining in tumor
cells but negative staining in
the osteoclast-like giant cells
(alkaline phosphatase stain)
37. Fibroblastic Osteosarcoma
(a) Clusters of moderately atypical spindle
cells embedded in osteoid-like matrix (MGG).
Small cell osteosarcoma.
(b) FNA smears.
(c) Cell block.
Small- to medium-sized tumor cells with
rounded nuclei and scanty cytoplasm
resembling Ewing sarcoma (H&E)
38. Parosteal Osteosarcoma
a rare type of low-grade osteosarcoma
arising on the surface of the bone.
Clusters of slightly atypical spindle cells
embedded in osteoid-like matrix (MGG).
40. Case – 4
20 year old women with h/o of pain in the
left shoulder since 2 weeks on and off .
X- ray showed well circumscribed
expansile osteolytic lesion situated in a
medullary location.
Punctate calcification or popcorn
appearance
42. Chondroma
Are benign cartilaginous neoplasms occurring within the bone
Involve small tubular bones of the hands and feet , femur and humerus.
Cytologic features
Cartilaginous fragments containing cells in lacunar spaces
Cells with small regular nuclei
Often slight cellular pleomorphism
Focal nuclear atypia and pleomorphism should not be mistaken for signs of malignancy.
Differential diagnosis – Grade I Chondrosarcoma
43. Case – 5
A 15 YEAR old boy comes with a history of right
knee swelling since 1 week and pain since 6
months .
X- ray showed – Oval, eccentric metaphyseal lesions
oriented parallel to the long axis of the bone , with
sharply defined margins with sclerotic and scalloped
borders displaying a lytic lesion.
45. Chondromyxoid fibroma
2nd – 3rd decade..
Chondromyxoid fibroma arises usually in the metaphyseal region of long tubular bones,
especially the tibia
Cytological features:
Myxoid background matrix
Cartilaginous fragments (with chondroblast-like cells in lacunae)
Dispersed or clustered stellate or spindle-shaped myofibroblastic cells
Osteoclastic giant cells
Differential diagnosis – Chondrosarcoma , Enchondroma and chondroblastoma.
46. Case – 6
28 year old female with h/ o hard
swelling and pain in the lower end of
right leg since 2 weeks.
X- ray showed – pedunculated lesion
growing over the surface of the bone
which is smoothly contoured bony stalk
continuous with adjacent cortex.
48. Osteochondroma
Never sampled by FNAC as its radiologic appearances are diagnostic.
Cytological features
1. Fragments o mature hyaline cartilage .The fragments have sharp borders and appear heavy bodied
with lacunar spaces.
2. Chondrocytes are seen best with PAP and H& E.
3. Cell blocks are useful in diagnosis.
Differential diagnosis – Parosteal osteosarcoma.
49. Case – 7
A15 year old child came to hospital with h/
o pain and swelling in the knee with his
parents complaining of limping of right leg
since 3 days.
X – ray showed sharply demarcated round
to oval epiphyseal lesions crossing
metaphysis with a rim of sclerotic bone.
50. Chondroblastoma
A rare, benign chondrogenic lesion
M:F = 2:1
80% of patients under 25 years of age
Cytological features
1. Mononuclear chondroblasts
characterized by well defined
cytoplasm and round nuclei
2. Multinucleated osteoclast-like cell
3. Fragments of chondroid matrix
4. The nucleus is grooved
51. Case – 8
70 year old man presented to OPD with
h/ o severe pain in left hip since 1 year
and more in the night.
X – ray – showed radiolucent areas in
the left Iliac bone containing moderate
amount of calcification.
52. Chondrosarcoma
GRADE I (WELL
DIFFERENTIATED)
low cellularity
fragments of hyaline cartilage
with lacunar spaces
containing neoplastic
chondrocytes.
Binucleated chondrocytes
are present
No mitotic figures seen.
Little or no myxoid –
chondroid matrix present.
53. Chondrosarcoma
GRADE II
Low to moderate cellularity.
Hyaline and myxoid –
chondroid matrix are
frequently abundant.
Neoplastic cells lie singly in
small clusters , within lacunar
spaces and in small sheets.
Occasinal small nucleoli .
54. Chondrosarcoma
GRADE III
Cellular smears with abundant
myxoid – chondroid stroma.
Mitotic figures present
Cells have single large cytoplasmic
vacuoles displacing the nucleus to
the periphery giving a signet- ring
appearance.
55. Mesenchymal chondrosarcoma
Aspirate – is gelatinous and blood tinged.
Cytological features
1. cellular , with rich myxoid chondroid background matrix.
2. Two cell populations – a small primitive appearing cells and cells showing chondrocytic
differentiation.
3. Focal necrosis and acute inflammation
4. The chondrocyte like cell population with moderate to abundant cytoplasm containing vacuoles.
5. The cells characterized by eccentric nuclei with coarsely granular chromatin and distinct
nucleoli.
Differential diagnosis – Small round cell malignancies , Intraosseous
hemangiopericytoma.
56. Mesenchymal chondrosarcoma
Clusters of small, round to oval tumor
cells with sparse cytoplasm and
irregular nuclei.
Cells embedded in a blue-violet
collagenous matrix (MGG).
57. Clear cell chondrosarcoma
Large epithelioid cells with abundant
finely vacuolated cytoplasm,
a central or paracentral nucleus,
fragments of cartilage, and
occasional osteoclast-like giant cells
(MGG)
60. Case - 9
35 year old woman with h/o slow
growing mass in left wrist since 1
year and pain since 4weeks.
X – ray showed – well defined
osteolytic lesion with incomplete
surrounding sclerosis with
multiloculated appearance .
62. Giant cell tumor
Cytological features
Hypercellular yield with both cohesive cell clusters and single cells.
Double-cell population: mononuclear spindle or round to ovoid cells and multinucleated
osteoclast-like giant cells.
Mononuclear cells contain nuclei with open chromatin and prominent nucleoli.
The size of mononuclear cell nuclei is comparable to that in the osteoclast-like giant cells.
Classical pattern of smears includes giant cells attached to the periphery of clusters of
mononuclear cells.
Absence of osteoid and cartilaginous matrix.
63. Differential diagnosis
Aneurysmal bone cyst
Brown tumor of hyperparathyroidism
Reparative giant cell granuloma
Osteoblastoma
Giant cell-rich osteosarcoma
64. Aneurysmal bone cyst
Multilocular, locally destructive lesion.
Age - < 20yrs.
Vertebral column, the craniofacial bones,
and metaphysis of long tubular bones.
X- Ray - seen as osteolytic , expansile,
eccentric lesions in metaphysis.
65. ABC cytology
Cytologic features
Hemorrhagic aspirates
Variable numbers of multinucleated giant
cells
Variable presence of clusters of spindled
myofibroblastic cells
Histiocytes and inflammatory cells
Lack of significant cytologic atypia
66. Brown Tumor of Hyperparathyroidism
X- Ray
Lytic lesion with irregular sclerosed
cortex
Differential diagnosis and problems
in diagnosis:
Conventional giant cell tumor
Aneurysmal bone cyst
Reparative giant cell granuloma
67. Brown Tumor of
Hyperparathyroidism
Cytologic features
Dispersed spindle cells or small- to
medium-sized clusters of spindle
cells
Osteoclast-like giant cells
Hemosiderin-laden macrophages
68. Giant Cell Reparative Granuloma
X- Ray – Osteolytic ,eccentric lesion in
the epiphysis without a sclerotic margin.
May show a soap bubble appearance.
69. Giant Cell Reparative Granuloma
Cytologic features:
Sheets and clusters of spindle cells
Multinucleated giant cells
Osteoblasts
Histiocytes
( a and b ) (MGG; H&E).
( c ) Cell block - (H&E)
70. VASCULAR LESIONS
Hemangioma – only blood is aspirated.
Strands of endothelial cells with spindled , bland nuclei may be found in smears .
Also seen are hemosiderin containing macrophages , osteoblasts and fibroblasts.
71. Cystic lesions of bone
Unicameral bone cyst
Aneurysmal bone cyst
Telangiectatic Osteosarcoma
Intraosseous ganglion cyst
Subchondral Osteoarthritic Bone cyst
Intraosseous Epidermal cysts.
73. Adamantinoma of long bones
2ND AND 6TH DECADE
M: f – 1.3 : 2
H/o dull aching pain with swelling.
X- Ray
Metaphysis / Diaphysis
Tibia / Fibula
Eccentric zone of lysis
Osteolytic area is bubbly / honeycomb
74. On cytology
Cellular smears with small clusters of cells
Majority are spindle shaped, some are
round to oval.
Distinct / absent cytoplasm
Necrotic debris in the background.
75. Intraosseous desmoplastic fibroma
3rd decade.
Mandible , pelvic bones and femur.
Swelling , tenderness and aching pain.
X- ray – shows Lytic appearance with
sclerotic margin.
Orthopantomograph well-defined
radiolucent lesion over the right
mandible
76. Cytology
Spindle shaped cells in clusters .
Collagen fiber debris
Bland nucleus with fine chromatin and small indistinct nucleoli.
No mitotic figures seen.
78. Case- 10
15 year old man with slow growing
mass in the left arm since 1 year with
redness and pain since 1 week.
X- RAY showed illdefined ,
permeative ,destructive
intramedullary lesion .Onion skin
appearance.
79. Ewings sarcoma - cytology
Cellular
Neoplastic cells with uniform size and
round shape
Bimodal population of – light & dark cells
Light cells – open chromatin
Dark cells – condensed chromatin
Glycogen / rosette like structures present
Scanty cytoplasm , appears as thin rim.
80. Non – hodgkins lymphoma
Very rare
> 40 yrs
Male predominance
X- ray
Lytic appearance
Permeative moth eaten pattern
Cortex is lysed with extension into
surrounding soft tissue.
Periosteal new bone formation – onion
skin peal appearance.
81. Cytology
Monorphous population of large lymphoid cells showing nuclear enlargement.
The background is dirty
Contains characteristic lymphoglandular bodies.
Atypical lymphocytes are 2- 3 times the size of small lymphocyte.
82. Langerhans cell histiocytosis
5 – 15 YRS
3:2
Skull , jaw , humerus, rib , femur.
Metaphysis or diaphysis.
Benign.
X- ray
Lytic masses that may extend into soft
tissue
83. Cytology
cellular with large, polygonal cells with ample
cytoplasm, nuclei are round, oval or bean
shaped with fine and even chromatin and
prominent longitudinal grooves
Inconspicuous nucleoli, mild pleomorphism
No / minimal mitotic figures
Scattered eosinophils and neutrophils and
multinucleated osteoclast-like giant cells
Necrosis common
85. Breast carcinoma mets to bone
usually appear in the medullary cavity,
spread to destroy the medullary bone, and
then involve the cortex
86. Cytology
Metastatic ductal carcinoma of the breast
shows cells arranged in loose clusters.
Inset. Details of nuclear morphology with
coarse chromatin and prominent irregular
nucleoli.
87. Carcinoma prostate
densely sclerotic osteoblastic metastases,
which frequently involve vertebral bodies and
the pelvis
Metastatic foci can be obliterated by a
pronounced osteoblastic reaction
88. Cytology
. A,B. Large cohesive sheets of prostatic
carcinoma cells.
the nuclei of the tumor cells are uniform
in size with minimal atypia.
prominent nucleoli, and evenly
distributed chromatin.
89. Carcinoma of lung
O15 % of carcinomas metastases to bone
Lytic lesions in bone
90. Cytology – mets of ca of lung
Clusters of the large lung
adenocarcinoma cells showing
obvious cytologic atypia
98. Reporting the diagnosis on bone
lesions
Sarcoma (histologic type of sarcoma or sarcoma not otherwise specified [NOS])
Benign tumor (histologic type or benign tumor NOS)
Metastasis (suggestion of primary or descriptive diagnosis)
Lymphohematologic malignancy (exact subtype defined or general classification as malignant
lymphoma, non-Hodgkin lymphoma)
Non neoplastic lesion (infectious, reactive)
Non diagnostic (including insufficient)
A standardized reporting of bone FNA has been suggested
by Åkerman et al.
99. To Summarize
Age , Clinical features, Specific site, Radiology , Clinical presentation and underlying
conditions.
FNA technique should be based on the location of the tumor.
Algorithm approach helps in making a appropriate diagnosis.
100.
101.
102. References
Cytopathology of bone and soft tissue tumors by Lester J Layfield
Current concepts in Bone and soft tissue tumors by Dr.Ajay Puri
Koss diagnostic cytology and its Histopathologic bases.
Atlas of Fine needle aspiration cytology by Henryk . A . Domanski.
Internet sources.
They are uniform cells of rounded or triangular shape, with abundant cytoplasm, which often contains a clear “hof” area adjacent to the nucleus. The round nuclei with a central nucleolus are situated very close to the cytoplasmic membrane giving impression of almost protruding through it (H&E and MGG)
Osteoclasts appear as scattered single large cells with abundant cytoplasm and multiple, uniform, round to oval nuclei. In (MGG)- a fine red cytoplasmic granulation is seen
Composed of a hyaline matrix, which is reddish blue to violet with MGG or pink with (H&E). Normal chondrocytes present infrequently as a single cell
Bone marrow cells. ( a and b ) Erythropoietic and myelopoietic cells and megakaryocytes appear occasionally in FNA smears from skeletal lesions. Megakaryocytes must not be misinterpreted as tumor cells (MGG)
Neoplastic chondrocytes are round to oval with moderate to abundant cytoplasm with enlarged nuclei and moderately to coarsely granular chromatin and one to two dinstinct nucleoli.
The cytoplasm may be vacuolated seen displacing the nucleus to the periphery of the cell.